Integrated approaches to decipher 3D genomes

项目总结 随着对基因组3D结构组织的更好的了解，澄清的挑战随之而来 哪些因素决定了这些结构，它们的功能含义是什么，这些结构是如何决定的 在细胞分化或疾病进展等细胞过程中被调节。蛋白质及其复合体 在协调染色质相互作用和染色体折叠方面发挥关键作用。因此，链接是很重要的 内源性蛋白质复合体的发现及其在特定染色质形成中的作用 互动。我们在这个部分的目标是开发一种新的技术来阐明蛋白质的作用 染色质折叠中的复合体。具体地说，我们将DNA-DNA邻近图谱与发现 潜在的因果蛋白质复合体。我们将开发“基因组构象捕获-蛋白质组”方法 (GCCP)用于同时检测染色质相互作用和相关的内源性蛋白质复合体。 我们将使用一条成熟的管道来分离天然蛋白质复合体，但针对 目的读出检测到的特异性蛋白质复合体周围的染色质相互作用体。

Project summary With better knowledge about the 3D structural organization of the genome comes the challenge of elucidating which factors determine these structures, what is their functional implications, and how are these structures modulated during cell processes such as cell differentiation or disease progression. Proteins and their complexes play critical roles in orchestrating chromatin interactions and chromosome folding. It is therefore important to link the discovery of endogenous protein complexes with their roles in the formation of specific chromatin interactions. Our goal in this component is to develop a new technology for elucidating the role of protein complexes in chromatin folding. Specifically we combine DNA-DNA proximity mapping with the discovery of the underlying causal protein complexes. We will develop the “Genome Conformation Capture-Proteome” method (GCCP) for simultaneous detection of chromatin interactions and associated endogenous protein complexes. We will employ a proven pipeline for the isolation of native protein complexes, but extensively optimized for the purpose of reading out the chromatin interactome surrounding the detected specific protein complexes.